Kai-Ming Zhang, Xiao-Min Wang, Angela M. Peterson, Wenride (clonidine) , an a2-adrenoceptor (a2AR) agonist, is reYan Chen, and Sukhbir S. Mokha. a2-Adrenoceptors modulate ported to be effective in treating neuropathic pain in humans NMDA-evoked responses of neurons in the superficial and deeper (Eisenach et al.1995; Tamsen and Gordh 1984) and in attendorsal horn of the medulla. J. Neurophysiol....

BACKGROUND Clonidine has been shown to be a potent neuroprotectant by acting at α(2) receptors on glutamatergic neurons to inhibit the release of glutamate. The aim of this study is to investigate the effects of clonidine on the activity of EAAT3 that can regulate extracellular glutamate. METHODS EAAT3 was expressed in the Xenopus oocytes. Using a two-electrode voltage clamp, membrane current...

Moxonidine, an antihypertensive imidazoline compound, reduces blood pressure by selective activation of central imidazoline I(1)-receptors and inhibition of sympathetic nerve activity and by direct actions on the kidney, with both mechanisms resulting in diuresis and natriuresis. We hypothesized that the hypotensive and renal actions of moxonidine may be mediated by atrial natriuretic peptide (...

1. I1 non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2. We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidin...

Clonidine (Catapres, Catapresan), guanfacine (Estulic), and methyldopa (Aldomet) are the prototypes of centrally acting antihypertensive drugs. Clonidine and guanfacine are lipophilic drugs that readily penetrate into the brain, where they stimulate alpha-adrenergic receptors in the pontomedullary region. The stimulation of these central alpha-adrenergic receptors has been shown to activate an ...

The population of reserve alpha-2 adrenoceptors that mediate the inhibitory effect of clonidine on the activity of locus coeruleus neurons has been studied using extracellular recordings in anesthetized rats. Animals were pretreated with the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1-2-dihydroquinoline (EEDQ). In rats pretreated with EEDQ (1, 2 and 6 mg/kg, i.p., 6 hr before e...

When coadministered spinally, morphine and clonidine interact synergistically to produce antinociception. The mechanism for the synergism is unknown, but may depend on intracellular messenger systems. Agents that alter the activities of protein kinases alter antinociception produced by opioids, but their effects on clonidine-induced antinociception or the morphine/clonidine interaction are not ...

Spinal administration of opioid and α2-adrenergic receptor (α2AR) agonists produces analgesia, and agonists interact synergistically when coadministered. The molecular mechanism underlying this synergy is largely unknown. Pharmacological studies have identified both the delta and the mu-opioid receptors (DOR and MOR) as candidate receptors capable of interacting synergistically with α2AR agonis...

BACKGROUND We have recently described the synthesis and circulatory properties of two novel centrally acting imidazoline agents: marsanidine (1-[(imidazolidin-2-yl)imino]indazole) and 7-Me-marsanidine (1-[(imidazolidin-2-yl)imino]-7-methylindazole). Marsanidine has proven to be a highly selective α2-adrenoceptor ligand with the α2/I1 selectivity ratio of 3879, while 7-Me-marsanidine has been sh...

Pan, Yu-Zhen, De-Pei Li, and Hui-Lin Pan. Inhibition of glutamatergic synaptic input to spinal lamina IIo neurons by presynaptic 2-adrenergic receptors. J Neurophysiol 87: 1938–1947, 2002; 10.1152/jn.00575.2001. Activation of spinal 2-adrenergic receptors by the descending noradrenergic system and 2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic actio...